The effect of ketanserin on cardiovascular reflexes in conscious normotensive and spontaneously hypertensive rats.
The effect of ketanserin (3 mg/kg i.v.) on the baroreceptor heart rate reflex and the Bezold-Jarisch reflex was examined in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the control situation (before ketanserin treatment), reflex bradycardia in response to phenylephrine (baroreflex) and phenyldiguanide (Bezold-Jarisch reflex) were impaired in SHR as compared with WKY, while reflex tachycardia in response to nitroprusside was similar in the two groups. However, after ketanserin administration in SHR, there was a reversal of the baroreflex-mediated tachycardia in response to nitroprusside into a bradycardic response. The nitroprusside-induced bradycardia was not caused by the release of 5-HT stimulating chemosensitive vagal afferents since the 5-HT3 receptor antagonist MDL 72222 did not block this response. In the same SHR, the Bezold-Jarisch reflex evoked by phenyldiguanide and the phenylephrine-induced bradycardia were potentiated by ketanserin. All the above effects of ketanserin were less evident in the WKY. Ketanserin did not alter vagal efferent function in anaesthetized SHR since it did not affect bradycardia induced by electrical stimulation of the vagus nerve. Therefore, it is suggested that ketanserin has sensitised cardiac vagal afferent mechanisms in SHR, which led to a normalization of reflex bradycardic function to a level normally observed in conscious normotensive WKY (i.e. prior to ketanserin treatment).
Widdop
R E
RE
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Verberne
A J
AJ
Louis
W J
WJ
Jarrott
B
B
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex / Q000187:drug effects*; D014326:Tropanes / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D001645:Biguanides; D007004:Hypoglycemic Agents; D014326:Tropanes; D009599:Nitroprusside; D001285:Atropine; D007650:Ketanserin; C042253:bemesetron; C008846:phenyl biguanide